Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences

Abstract

Peptides with broad-spectrum antimicrobial activity are found in the mucosal surfaces at many sites in the body, including the airway, the oral cavity, and the digestive tract. Based on their in vitro antimicrobial and other immunomodulatory activities, these host defense peptides have been proposed to play an important role in the innate defense against pathogenic microbial colonization. The genes that encode these peptides are up-regulated by pathogens, further supporting their role in innate immune defense. However, the differences in the local microbial environments between the generally sterile airway and the highly colonized oral cavity suggest a more complex role for these peptides in innate immunity. For example, β-defensin genes are induced in the airway by all bacteria and Toll-like receptor (TLR) agonists primarily through an NF-κB-mediated pathway. In contrast, the same genes are induced in the gingival epithelium by only a subset of bacteria and TLR ligands, via different pathways. Furthermore, the environments into which the peptides are secretedspecifically saliva, gingival crevicular fluid, and airway surface fluid-differ greatly and can effect their respective activities in host defense. In this review, we examine the differences and similarities between host defense peptides in the oral cavity and the airway, to gain a better understanding of their contributions to immunity.

Epithelial Cells and Innate Antifungal Defense

“…In general, pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNF, GM-CSF, and others) regulate leukocyte trafficking (Eversole et al, 1997) and/or activate a strong antifungal response by these cells (DongariBagtzoglou et al, 2005). In addition, oral epithelial cells are capable of inducing antimicrobial peptides, such as defensins, cathelicidins, and histatins (reviewed in Diamond et al, 2008), which control C. albicans growth and infection. Among these peptides, human β-defensin-2 (hBD-2), hBD-3 (Joly et al, 2004;Feng et al, 2005;Schneider et al, 2005), LL-37 (Turner et al, 1998), and histatin-5 (Oppenheim et al, 1988) exhibit potent anti-candidal properties.…”

Potential of the Phytomedicine Echinacea in the Treatment of Pulmonary Infections and Bronchitis

“…Thus, the epithelium has a two-fold function in response to potential pathogens; it has a barrier function and also serves as a sensor that signals an efficient antimicrobial response. This is the primary component of the innate "immune" or "non-specific" host response (Diamond et al, 2008;Evans et al, 2010). However, incomplete elimination of the pathogen, or over-stimulation of the responses, can lead to an excessive or chronic inflammatory condition.…”

“…Chronic bronchitis may also be exacerbated by the same agents. These viruses and bacteria initially encounter epithelial tissues of the nose, oral mucosa, bronchi and airway linings, which are composed primarily of epithelial cells covered by a "soup" of proteins, glycoproteins, muco-polysaccharides, some of which possess intrinsic antimicrobial properties (Diamond et al, 2008;Evans et al, 2010). Interspersed among these epithelial cells are occasional phagocytes and various types of leukocyte.…”

Innate immune cell response uponCandida albicansinfection

“…6 These host defense peptides have been recognized as important antimicrobial effectors in innate immune responses but may result in different respective activities if released into different local microbial environments. 80 It is well worth mentioning the protective effect of Th17 responses which mediate the production of IL-17 and IL-22. IL-17 and IL-22 both contribute to clear mucosal candidal infections by upregulating the expression the antimicrobial peptides by oral epithelial cells.…”